Metformin administration during pregnancy — current insight

The main mechanism of gestational diabetes mellitus (GDM) is insulin resistance, therefore using metformin as a medicinereducing insulin resistance appears to be promising.Currently, the majority of medical associations do not recommend using metformin during pregnancy as the first-line oftherapy when the diet regimen is insufficient for glycaemic control. However, they do allow its administration if there isno possibility of insulin treatment.There is some evidence which suggests that using metformin during pregnancy is not related to an increased risk of obstetriccomplications during delivery and that its influence on the foetus can be beneficial.Since metformin crosses the placenta, the major argument for cautious use of this drug are the potential long-term effectsof the treatment for the child and its development in later life.In this article, the authors attempt to discuss the use of metformin during pregnancy and the safety of the treatment inthe light of current studies and recommendations

Transcriptomic Dysregulation of Inflammation-Related Genes in Leukocytes of Patients with Gestational Diabetes Mellitus (GDM) during and after Pregnancy: Identifying Potential Biomarkers Relevant to Glycemic Abnormality

Although the immune system has been implicated in the pathophysiology of gestational diabetes mellitus (GDM) and postpartum abnormal glucose tolerance (AGT), little is known about the transcriptional response of inflammation-related genes linked to metabolic phenotypes of GDM women during and after pregnancy, which may be potential diagnostic classifiers for GDM and biomarkers for predicting AGT. To address these questions, gene expression of IL6, IL8, IL10, IL13, IL18, TNFA, and the nuclear factor κB (NFκB)/RELA transcription factor were quantified in leukocytes of 28 diabetic women at GDM diagnosis (GDM group) and 1-year postpartum (pGDM group: 10 women with AGT and 18 normoglycemic women), using a nested RT-PCR method. Control pregnancies with normal glucose tolerance (NGT group; n = 31) were closely matched for maternal age, gestational age, pre-pregnancy BMI, pregnancy weight, and gestational weight gain. Compared with the NGT group, IL8 was downregulated in the GDM group, and IL13 and RELA were upregulated in the pGDM group, whereas IL6, IL10, and IL18 were upregulated in the GDM and pGDM groups. The TNFA level did not change from pregnancy to postpartum. Associations of some cytokines with glycemic measures were detected in pregnancy (IL6 and RELA) and postpartum (IL10) (p < 0.05). Receiver operating characteristic (ROC) curves showed that IL6, IL8, and IL18, if employed alone, can discriminate GDM patients from NGT individuals at GDM diagnosis, with the area under the ROC curves (AUCs) of 0.844, (95% CI 0.736–0.953), 0.771 (95% CI 0.651–0.890), and 0.714 (95% CI 0.582–0.846), respectively. By the logistic regression method, we also identified a three-gene panel (IL8, IL13, and TNFA) for postpartum AGT prediction. This study demonstrates a different transcriptional response of the studied genes in clinically well-characterized women with GDM at GDM diagnosis and 1-year postpartum, and provides novel transcriptomic biomarkers for future efforts aimed at diagnosing GDM and identifying the high risk of postpartum AGT groups

Parity does not affect diabetes complications in women with type 1 diabetes

Introduction The problem concerning the impact of pregnancy on diabetic complications is a matter for discussion as there is some evidence suggesting that pregnancy may trigger development or progression of diabetic chronic complications. However, currently available data concerning this issue is still controversial. Objective The aim of the study was to evaluate the impact of obstetric history on the development of chronic microangiopatic and macroangiopatic complications in type 1 diabetic women. Material and Methods The retrospective study comprised 226 white Caucasian type 1 diabetic women, including 190 parous and 36 nulliparous women. Anthropometric data, information concerning the course of the disease, including metabolic control and chronic complications, together with obstetric history, were registered. Results Parous women were older (p 0.05) and diabetes duration (p>0.05) from nulliparous subjects. There were no significant differences in the incidence (p>0.05) nor onset (p>0.05) of chronic diabetes complications between the groups. The number of deliveries did not correlate with either the incidence nor the onset of chronic complications. Longer DM duration at the moment of first delivery was related to the higher incidence of retinopathy (p<0.01), nephropathy (p<0.05) and neuropathy (p<0.001). Conclusions The incidence of chronic diabetic complications does not differ between parous women and the subjects that were never pregnant, and is not related to the number of pregnancies

Expression Profile of Diabetes-Related Genes Associated with Leukocyte Sirtuin 1 Overexpression in Gestational Diabetes

Although compelling evidence indicates that Sirtuin 1 (SIRT1) plays a prominent role in type 2 diabetes, its relationship with gestational diabetes (GDM) remains elusive. This study was aimed at identifying diabetes-related genes and cellular pathways linked to changes of leukocyte SIRT1 expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte SIRT1 expression, and two subgroups were distinguished, namely GDM/SIRT1(&#8593;) (n = 30, p &lt; 0.05) and GDM/SIRT1(&#8596;) (n = 92, p &gt; 0.05), with significant and insignificant changes in leukocyte SIRT1 expression compared to a normal glucose tolerant (NGT) group (n = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a &#177; 2-fold difference in expression in GDM/SIRT1(&#8593;) patients (n = 9) vs. NGT controls (n = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/SIRT1(&#8593;) group and the whole NGT group (p &lt; 0.05). Interestingly, of these four genes, only ACLY expression was found to significantly differ between GDM/SIRT1(&#8593;) and GDM/SIRT1(&#8596;). This study demonstrates that under hyperglycemic conditions, leukocyte SIRT1 overexpression is accompanied by an over-abundance of three transcripts and an under-abundance of another; these four govern related metabolism, inflammation, and transport functions, suggesting that such alterations might represent systemic biological adaptations with a unique ACLY under-expression in GDM/SIRT1(&#8593;) women

Lipid profile changes in erythrocyte membranes of women with diagnosed GDM.

Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring